A Homolytic Substitution Approach for Directing Group-Free Nickel-Catalyzed Dialkylation of Unactivated Alkenes

Abstract

The selective construction of two C(sp³)–C(sp³) bonds through trimolecular cross-coupling of unactivated alkenes remains one of the most difficult challenges in organic synthesis. Despite previous advances in metal-catalyzed coupling for the dicarbofunctionalization of alkenes, dialkylation is still problematic due to the instability of the requisite metal–alkyl intermediate, which undergoes facile β-hydride elimination or protodemetalation. Recently, our group was successful in developing a bimolecular homolytic substitution (S_H2) strategy that circumvents metal–alkyl side reactions and accomplishes the challenging cross-coupling of metal–alkyl intermediates with alkyl radicals in the absence of a directing auxiliary, permitting a highly regioselective dialkylation of unactivated alkenes.

1 Introduction

2 Nickel-Catalyzed Dicarbofunctionalization of Unactivated Alkenes

3 Nickel-Catalyzed Dialkylation of Unactivated Alkenes

4 Conclusions and Perspectives

Key words

nickel catalysis - dialkylation - unactivated alkenes - bimolecular homolytic substitution - radicals

Publication History

Received: 28 May 2024

Accepted after revision: 25 June 2024

Accepted Manuscript online:
25 June 2024

Article published online:
15 July 2024

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